RESUMO
O mastocitoma é uma das neoplasias cutâneas mais comuns que acometem cães. O diagnóstico da doença é baseado em aspectos clínicos e laboratoriais, sendo a citologia e a histopatologia os métodos de eleição. Diante disso, o objetivo deste estudo é relatar a importância da ampla abordagem diagnóstica de mastocitoma cutâneo metastático em uma fêmea canina castrada, atendida no Hospital Veterinário da Universidade Estadual do Ceará, com uma neoformação em membro compatível com mastocitoma. O estadiamento da paciente foi feito através de exames laboratoriais de hemograma completo, e citologia aspirativa de linfonodo regional e medula óssea, que evidenciaram a presença de focos de metástase; bem como do exame de ultrassom abdominal, que evidenciou alterações no parênquima hepático e linfoadenomegalia ilíaco medial direita. Diante das suspeitas, optou-se pela eutanásia da paciente, cujo corpo foi enviado para os exames de necropsia e histopatologia, os quais confirmaram o diagnóstico de mastocitoma cutâneo de alto grau, com metástase em fígado, pulmão, medula e linfonodos. Desta forma pode-se concluir que o mastocitoma cutâneo metastático é uma neoplasia de diagnóstico multifatorial, em que a realização de exames hematológicos associados às análises citológicas, histopatológicas e de imagem são indispensáveis para estabelecer o diagnóstico definitivo para que seja determinada uma melhor conduta terapêutica e prognóstico de pacientes caninos.
Mast cell tumors are one of the most common skin neoplasms that affect dogs. The diagnosis is based on clinical and laboratory aspects, with cytology and histopathology being the preferred methods. Therefore, this study aims to report the importance of the broad diagnostic approach of metastatic cutaneous mastocytoma in a castrated a female dog attended at the Veterinary Hospital of the State University of Ceará, with a neoformation in a member compatible with mast cell tumor. The patient's staging was performed through laboratory tests of complete blood count, aspiration cytology of regional lymph nodes and bone marrow, which showed the presence of focus of metastasis, as well as the abdominal ultrasound examination, which showed changes in the liver parenchymas and right medial iliac lymphadenopathy. Given the suspicions, the patient was euthanized and the body was sent for necropsy and histopathological examination, which confirmed the diagnosis of high-grade cutaneous mast cell tumor, with metastasis in the liver, lung, bone marrow, and lymph nodes. Thus, it can be is concluded that mast cell tumor is a neoplasm of multifactorial diagnosis, where hematological tests associated with cytology, histopathological, and imaging analyses are essential to establish the definitive diagnosis to determine a better therapeutic behavior and prognosis of canine patients.
Assuntos
Animais , Feminino , Cães , Mastocitoma Cutâneo/diagnóstico , Mastocitoma Cutâneo/veterinária , Mastócitos/citologia , Contagem de Células Sanguíneas/veterinária , Metástase Neoplásica/diagnósticoRESUMO
Mast cells are tissue-resident, innate immune cells that play a key role in the inflammatory response and tissue homeostasis. Mast cells accumulate in the tumor stroma of different human cancer types, and increased mast cell density has been associated to either good or poor prognosis, depending on the tumor type and stage. Mast cells play a multifaceted role in the tumor microenvironment by modulating various events of tumor biology, such as cell proliferation and survival, angiogenesis, invasiveness, and metastasis. Moreover, tumor-associated mast cells have the potential to shape the tumor microenvironment by establishing crosstalk with other tumor-infiltrating cells. This chapter reviews the current understanding of the role of mast cells in the tumor microenvironment. These cells have received much less attention than other tumor-associated immune cells but are now recognized as critical components of the tumor microenvironment and could hold promise as a potential target to improve cancer immunotherapy.
Assuntos
Mastócitos/citologia , Neoplasias/imunologia , Microambiente Tumoral/imunologia , Humanos , Mastócitos/imunologiaRESUMO
Mast cell activation through the high-affinity IgE receptor (FcεRI) plays a central role in allergic reactions. FcεRI-mediated activation triggers multiple signaling pathways leading to degranulation and synthesis of different inflammatory mediators. IgE-mediated mast cell activation can be modulated by different molecules, including several drugs. Herein, we investigated the immunomodulatory activity of the histone deacetylase inhibitor valproic acid (VPA) on IgE-mediated mast cell activation. To this end, bone marrow-derived mast cells (BMMC) were sensitized with IgE and treated with VPA followed by FcεRI cross-linking. The results indicated that VPA reduced mast cell IgE-dependent degranulation and cytokine release. VPA also induced a significant reduction in the cell surface expression of FcεRI and CD117, but not other mast cell surface molecules. Interestingly, VPA treatment inhibited the phosphorylation of PLCγ2, a key signaling molecule involved in IgE-mediated degranulation and cytokine secretion. However, VPA did not affect the phosphorylation of other key components of the FcεRI signaling pathway, such as Syk, Akt, ERK1/2, or p38. Altogether, our data demonstrate that VPA affects PLCγ2 phosphorylation, which in turn decreases IgE-mediated mast cell activation. These results suggest that VPA might be a key modulator of allergic reactions and might be a promising therapeutic candidate.
Assuntos
Inibidores de Histona Desacetilases/farmacologia , Imunoglobulina E/imunologia , Mastócitos/efeitos dos fármacos , Fosfolipase C gama/antagonistas & inibidores , Receptores de IgE/efeitos dos fármacos , Ácido Valproico/farmacologia , Animais , Degranulação Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Interleucina-13/metabolismo , Interleucina-6/metabolismo , Mastócitos/citologia , Camundongos , Fosfolipase C gama/fisiologia , Receptores de IgE/biossíntese , Receptores de IgE/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Mast cells are connective tissue resident cells with morphological and functional characteristics that contribute to their role in allergic and inflammatory processes, host defense and maintenance of tissue homeostasis. Mast cell activation results in the release of pro-inflammatory mediators which are largely responsible for the physiological functions of mast cells. The lectin ArtinM, extracted from Artocarpus heterophyllus (jackfruit), binds to D-manose, thus inducing degranulation of mast cells. ArtinM has several immunomodulatory properties including acceleration of wound healing, and induction of cytokine release. The aim of the present study was to investigate the role of ArtinM in the activation and proliferation of mast cells. The rat mast cell line RBL-2H3 was used throughout this study. At a low concentration (0.25µg/mL), ArtinM induced mast cell activation and the release of IL-6 without stimulating the release of pre-formed or newly formed mediators. Additionally, when the cells were activated by ArtinM protein tyrosine phosphorylation was stimulated. The low concentration of ArtinM also activated the transcription factor NFkB, but not NFAT. ArtinM also affected the cell cycle and stimulated cell proliferation. Therefore, ArtinM may have therapeutic applications by modulating immune responses due to its ability to activate mast cells and promote the release of newly synthesized mediators. Additionally, ArtinM could have beneficial effects at low concentrations without degranulating mast cells and inducing allergic reactions.
Assuntos
Degranulação Celular/efeitos dos fármacos , Lectinas/farmacologia , Proteínas de Plantas/farmacologia , Animais , Artocarpus/metabolismo , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Membrana Celular/ultraestrutura , Proliferação de Células/efeitos dos fármacos , Interleucina-6/metabolismo , Mastócitos/citologia , Mastócitos/metabolismo , Mitose/efeitos dos fármacos , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , RatosRESUMO
Bauhinia forficata is a medicinal plant that has flavonoid components with hypoglycemic, antioxidant, hepatoprotective, antibacterial, antiviral and anti-inflammatory action. Aim of this study is to evaluate the action of B. forficata alcoholic extract in the male genital system of adult male Wistar rats. For that, 20 adult male Wistar rats were distributed into two experimental groups: the B. forficata group, receiving B. forficata alcoholic extract (0.1 ml/10 g body weight/day) on alternate days, and the control group, receiving just the vehicle for 30 days straight both via gavage. On the 31st day, the animals were euthanized, and the testis and epididymis were collected for histopathological, biochemical, morphometric, and sperm count analysis. Mass spectrometry identified new compounds in the extract: trans-caffeic acid, liquiritigenin, gallocatechin, and 2,4,6-trihydroxyphenanthren-2-glycoside. Biochemical analysis showed higher total cholesterol levels in the testis and lower malondialdehyde levels in the testis and epididymis, in the B. forficata group. The mast cell count showed a reduction in degranulated mast cells in the caput region of the epididymis, in the B. forficata group. The luminal compartment of the caput and the epithelial of the epididymis cauda were reduced, whereas the stromal region of the epididymis caput was increased in the B. forficata group, compared with the control group. The testicular tissue was less impaired, considering that all the histological analyses were similar to the control. We believe that B. forficata alcoholic extract in the male genital system showed antioxidant action, especially in the epididymal tissue.
Assuntos
Antioxidantes/farmacologia , Bauhinia/química , Epididimo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Testículo/metabolismo , Animais , Degranulação Celular/efeitos dos fármacos , Colesterol/análise , Masculino , Malondialdeído/análise , Mastócitos/citologia , Fitoterapia , Ratos , Ratos WistarRESUMO
In Colombia the use of glyphosate commercial formulations (Roundup) for spraying have left deleterious effects on animals and humans. Much of this spraying takes place at the Orinoco basin, habitat of one of the most exported ornamental fish in Colombia, Cardinal neon. To evaluate the effect of Roundup Activo four experimental treatments were carried out with 0 mg/L (T1), 0.1 mg/L (T2), 1 mg/L (T3) and 5 mg/L (T4) during 30 days of exposure. The fishes were processed for high-resolution optical microscopy. The main finding of Roundup Activo exposure was an increase in mast cells number in brain blood vessels and some neuronal nuclei of the preoptic and posterior diencephalic areas, including hypothalamus. A correlation between concentrations and mast cells number was observed, with the largest mast cells number in T4 treatment. Mast cells presence is a stress benchmark, suggesting the beginning of allergic, inflammatory and apoptotic events. Presence of mast cells in these brain areas may lead to alterations on reproduction, visual and olfactory information integration among other processes. These alterations may result in diminished survival, affecting the conservation of this species in its natural habitat.(AU)
En Colombia, el uso de formulaciones comerciales de glifosato (Roundup) para la fumigación ha producido efectos nocivos en animales y humanos. Gran parte de esta fumigación se realiza en la cuenca del Orinoco, hábitat de uno de los peces ornamentales más exportados de Colombia, el Neón Cardenal. Para evaluar el efecto de Roundup Activo se realizó un experimento con cuatro tratamientos 0 mg/L (T1), 0,1 mg/L (T2), 1 mg/L (T3) y 5 mg/L (T4) durante 30 días. Los peces fueron procesados para microscopía óptica de alta resolución. El principal hallazgo fue el aumento del número de mastocitos en los vasos sanguíneos cerebrales y algunos núcleos neuronales del área preóptica y diencefálica posterior, incluido el hipotálamo. Identificamos una correlación entre las concentraciones y el número de mastocitos, que alcanzó su máximo en T4. La presencia de mastocitos evidencia estrés, promoviendo eventos alérgicos, inflamatorios y apoptóticos. La presencia de mastocitos en estas áreas del cerebro puede llevar a alteraciones en la reproducción e integración de la información visual y olfativa entre otros procesos. Estas alteraciones pueden resultar en una disminución de la supervivencia, afectando la conservación de esta especie en su hábitat natural.(AU)
Assuntos
Animais , Caraciformes/fisiologia , Mastócitos/citologia , HerbicidasRESUMO
In Colombia the use of glyphosate commercial formulations (Roundup™) for spraying have left deleterious effects on animals and humans. Much of this spraying takes place at the Orinoco basin, habitat of one of the most exported ornamental fish in Colombia, Cardinal neon. To evaluate the effect of Roundup Activo™ four experimental treatments were carried out with 0 mg/L (T1), 0.1 mg/L (T2), 1 mg/L (T3) and 5 mg/L (T4) during 30 days of exposure. The fishes were processed for high-resolution optical microscopy. The main finding of Roundup Activo™ exposure was an increase in mast cells number in brain blood vessels and some neuronal nuclei of the preoptic and posterior diencephalic areas, including hypothalamus. A correlation between concentrations and mast cells number was observed, with the largest mast cells number in T4 treatment. Mast cells presence is a stress benchmark, suggesting the beginning of allergic, inflammatory and apoptotic events. Presence of mast cells in these brain areas may lead to alterations on reproduction, visual and olfactory information integration among other processes. These alterations may result in diminished survival, affecting the conservation of this species in its natural habitat.(AU)
En Colombia, el uso de formulaciones comerciales de glifosato (Roundup™) para la fumigación ha producido efectos nocivos en animales y humanos. Gran parte de esta fumigación se realiza en la cuenca del Orinoco, hábitat de uno de los peces ornamentales más exportados de Colombia, el Neón Cardenal. Para evaluar el efecto de Roundup Activo™ se realizó un experimento con cuatro tratamientos 0 mg/L (T1), 0,1 mg/L (T2), 1 mg/L (T3) y 5 mg/L (T4) durante 30 días. Los peces fueron procesados para microscopía óptica de alta resolución. El principal hallazgo fue el aumento del número de mastocitos en los vasos sanguíneos cerebrales y algunos núcleos neuronales del área preóptica y diencefálica posterior, incluido el hipotálamo. Identificamos una correlación entre las concentraciones y el número de mastocitos, que alcanzó su máximo en T4. La presencia de mastocitos evidencia estrés, promoviendo eventos alérgicos, inflamatorios y apoptóticos. La presencia de mastocitos en estas áreas del cerebro puede llevar a alteraciones en la reproducción e integración de la información visual y olfativa entre otros procesos. Estas alteraciones pueden resultar en una disminución de la supervivencia, afectando la conservación de esta especie en su hábitat natural.(AU)
Assuntos
Animais , Caraciformes/fisiologia , Mastócitos/citologia , HerbicidasRESUMO
Our aim was to evaluate whether postnatal exposure to a glyphosate-based herbicide (GBH) modifies mammary gland development in pre- and post-pubertal male rats. From postnatal day 1 (PND1) to PND7, male rats were injected subcutaneously every 48â¯h with either saline solution (vehicle) or 2â¯mg GBH/kg·bw. On PND21 and PND60, mammary gland and blood samples were collected. Estradiol (E2) and testosterone (T) serum levels, mammary gland histology, collagen fiber organization, mast cell infiltration, proliferation index, and estrogen (ESR1) and androgen receptor (AR) expression levels were evaluated. At PND21, GBH-exposed male rats exhibited greater development of the mammary gland with increased stromal collagen organization and terminal end buds (TEBs) compared to control rats. At PND60, the number of TEBs remained high and was accompanied by an increase in mast cell infiltration, proliferation and ESR1 expression in GBH-exposed male rats. In contrast, no effects were observed in E2 and T serum levels and AR expression in both days studied. Our results showed that a postnatal subacute treatment with GBH induces endocrine-disrupting effects in the male mammary gland in vivo, altering its normal development.
Assuntos
Glicina/análogos & derivados , Herbicidas/toxicidade , Glândulas Mamárias Animais/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Proliferação de Células , Estradiol/sangue , Receptor alfa de Estrogênio/metabolismo , Feminino , Glicina/toxicidade , Masculino , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/crescimento & desenvolvimento , Glândulas Mamárias Animais/metabolismo , Mastócitos/citologia , Ratos Wistar , Receptores Androgênicos/metabolismo , Maturidade Sexual , Testosterona/sangue , Testes de Toxicidade Subaguda , GlifosatoRESUMO
Angiogenesis is a complex process that involves interactions between endothelial cells and various other cell types as well as the tissue microenvironment. Several previous studies have demonstrated that mast cells accumulate at angiogenic sites. In spite of the evidence suggesting a relationship between mast cells and angiogenesis, the association of mast cells and endothelial cells remains poorly understood. The present study aims to investigate the relationship between mast cells and endothelial cells during in vitro angiogenesis. When endothelial cells were co-cultured with mast cells, angiogenesis was stimulated. Furthermore, there was direct intercellular communication via gap junctions between the two cell types. In addition, the presence of mast cells stimulated endothelial cells to release angiogenic factors. Moreover, conditioned medium from the co-cultures also stimulated in vitro angiogenesis. The results from this investigation demonstrate that mast cells have both direct and indirect proangiogenic effects and provide new insights into the role of mast cells in angiogenesis.
Assuntos
Comunicação Celular/fisiologia , Neovascularização Fisiológica/fisiologia , Indutores da Angiogênese/metabolismo , Animais , Linhagem Celular , Movimento Celular , Técnicas de Cocultura , Conexina 43/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Junções Comunicantes/metabolismo , Mastócitos/citologia , Mastócitos/metabolismo , Camundongos , Microscopia EletrônicaRESUMO
The objective of this study was to compare mast cell density (MCD) in oral epithelial dysplasias (OED) and oral squamous cell carcinoma (OSCC) and determine its correlation with clinical and histopathologic parameters and the degree of tumor differentiation. Thirty OSCC samples, 14 OED samples, and 4 non-neoplastic oral mucosa samples were analyzed by immunohistochemistry to determine MCD based on the expression of MC tryptase. In addition, MCs were categorized morphologically into degranulated and granulated cells. MCD was significantly higher in OSCC lesions with a greater degree of differentiation (P=0.04). No significant difference in MCD was detected between mild and moderate OED samples (P=0.09). Our findings indicate that MCs are present in the tumor microenvironment and may be associated with a better prognosis.
Assuntos
Carcinoma de Células Escamosas/patologia , Mastócitos/citologia , Mucosa Bucal/patologia , Neoplasias Bucais/patologia , Microambiente Tumoral , Biomarcadores Tumorais , Contagem de Células , Diferenciação Celular , Humanos , Imuno-Histoquímica , PrognósticoRESUMO
Mast cells are multifunctional immune cells that participate in many important processes such as defense against pathogens, allergic reactions, and tissue repair. These cells perform their functions through the release of a wide variety of mediators. This release occurs mainly through cross-linking IgE (immunoglobulin E) bound to high affinity IgE receptors by multivalent antigens. The abundance of mast cells in connective tissue, surrounding blood vessels, and their involvement in the early stages of bone repair support the possibility of physiological and pathological interactions between mast cells and osteoblasts. However, the participation of mast cell mediators in osteogenesis is not fully understood. Therefore, the objective of this work was to investigate the role of mast cell mediators in the acquisition of the osteogenic phenotype in vitro. The results show that pooled mast cell mediators can affect proliferation, morphology, and cytoskeleton of osteoblastic cells, and impair the activity and expression of alkaline phosphatase as well as the expression of bone sialoprotein. Also, mast cell mediators inhibit the expression of mRNA for those proteins and inhibit the formation and maturation of calcium nodules and consequently inhibit mineralization. Therefore, mast cell mediators can modulate osteogenesis and are potential therapeutic targets for treatments of bone disorders.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Mastócitos/citologia , Mastócitos/efeitos dos fármacos , Minerais/metabolismo , Osteoblastos/citologia , Citoesqueleto de Actina/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Fosfatase Alcalina/genética , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Sialoproteína de Ligação à Integrina/genética , Sialoproteína de Ligação à Integrina/metabolismo , Mastócitos/metabolismo , Osteoblastos/efeitos dos fármacos , Osteopontina/genética , Transporte Proteico/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RatosRESUMO
Titanium is a biomaterial widely used in dental and orthopedic implants. Since tissue-implant interactions occur at the nanoscale level, nanotextured titanium surfaces may affect cellular activity and modulate the tissue response that occurs at the tissue-implant interface. Therefore, the characterization of diverse cell types in response to titanium surfaces with nanotopography is important for the rational design of implants. Mast cells are multifunctional cells of the immune system that release a range of chemical mediators involved in the inflammatory response that occurs at the tissue-implant interface. Therefore, the aim of this study was to investigate the effects of the nanotopography of titanium surfaces on the physiology of mast cells. The results show that the nanotopography of titanium surfaces promoted the spreading of mast cells, which was accompanied by the reorganization of the cytoskeleton. Also, the nanotopography of titanium surfaces enhanced cell migration and cell growth, but did not alter the number of adherent cells in first hours of culture or affect focal adhesions and mediator release. Thus, the results show that nanotopography of titanium surfaces can affect mast cell physiology, and represents an improved strategy for the rational production of surfaces that stimulate tissue integration with the titanium implants. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2150-2161, 2017.
Assuntos
Materiais Biocompatíveis/química , Mastócitos/citologia , Nanoestruturas/química , Titânio/química , Animais , Adesão Celular , Linhagem Celular , Movimento Celular , Proliferação de Células , Ratos , Propriedades de SuperfícieRESUMO
Mast cells (MCs) participate in all stages of skin healing and one of their mediators is the Annexin A1 protein (AnxA1), linked to inflammation, proliferation, migration and apoptosis processes, but not studied in thermal burns yet. Therefore, our objectives were to evaluate the behavior of MCs and AnxA1 in a second degree burn model, treated or not with silver sulfadiazine 1% (SDP 1%) and associated to macrophages quantification and cytokines dosages. MCs counts showed few cells in the early stages of repair but increased MCs in the final phases in the untreated group. The normal skin presented numerous tryptase-positive MCs that were reduced after burning in all analyzed periods. Differently, few chymase-positive MCs were observed in the early stages of healing, however, increased chymase-positive MCs were found at the final phase in the untreated group. MCs also showed high immunoreactivity for AnxA1 on day 3 in both groups. In the tissue there was a strong protein expression in the early stages of healing, but in the final phases only in the SDP treated animals. TNF-α, IL-1ß, IL-6, IL-10 and MCP-1 levels and macrophages quantification were increased in inflammation and reepithelialization phases. Reduced IL-1ß, IL-6 and IL-10 levels and numerous macrophages occurred in the treated animals during tissue repair. Our results indicate modulation in the profile of MCs and AnxA1expression during healing by the treatment with SDP 1%, pointing them as targets for therapeutic interventions on skin burns.
Assuntos
Anexina A1/metabolismo , Queimaduras/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Mastócitos/citologia , Mastócitos/efeitos dos fármacos , Sulfadiazina de Prata/farmacologia , Animais , Queimaduras/imunologia , Queimaduras/metabolismo , Queimaduras/fisiopatologia , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Derme/efeitos dos fármacos , Derme/patologia , Modelos Animais de Doenças , Epiderme/efeitos dos fármacos , Epiderme/patologia , Histamina/metabolismo , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Ratos , Ratos Wistar , Sulfadiazina de Prata/uso terapêutico , Cicatrização/efeitos dos fármacosRESUMO
Bites caused by Scolopendra viridicornis centipede are mainly characterized by burning pain, paresthesia and edema. On this regard, the aim of this work was to study the involvement of mast cells and histamine in edema induced by Scolopendra viridicornis (Sv) centipede venom. The edema was analyzed on mice paws. The mice were pretreated with cromolyn (mast cell degranulation inhibitor) and antagonists of histamine receptors, such as promethazine (H1R), cimetidine (H2R) and thioperamide (H3/H4R). The analyses were carried out at different times after the injection of Sv venom (15 µg) or PBS in the footpad of mice. Our results showed a significant inhibition of the edema induced by Sv venom injection in mice previously treated: cromolyn (38-91%), promethazine (50-59%) and thioperamide (around 30%). The treatment with cimetidine did not alter the edema induced by Sv venom. Histopathological analysis showed that Sv venom injection (15 µg) induced edema, leukocyte recruitment and mast cells degranulation, when compared with the PBS-injected mice. Direct effects of the Sv venom on mast cells were studied in PT-18 line (mouse mast cell) and RBL-2H3 cells (rat mast cells). The data showed that higher doses (3.8 and 7.5 µg) of Sv venom were cytotoxic for both cell lineages and induced morphological changes. However, lower doses of the venom induced degranulation of both mast cell lines, as well as the secretion of MCP-1, IL-6 and IL-1ß. The production of PGD2 was only observed in the RBL-2H3 line incubated with Sv venom. Taking our results together, we demonstrated that upon Sv venom exposure, mast cells and histamine are crucial for the establishment of the local inflammatory reaction.
Assuntos
Venenos de Artrópodes/toxicidade , Edema/etiologia , Histamina/efeitos adversos , Mastócitos/citologia , Animais , Artrópodes , Linhagem Celular , Quimiocinas/biossíntese , Citocinas/biossíntese , Eicosanoides/biossíntese , Masculino , Mastócitos/metabolismo , Camundongos , Microscopia Eletrônica de VarreduraRESUMO
Puberty is characterized by psychosomatic alterations, whereas chronic ethanol consumption is associated with morphophysiological changes in the male reproductive system. The purpose of this study was to show the toxic effects on testis and epididymal morphophysiology after ethanol administration during peripuberty. To this end, male Wistar rats were divided into two groups: ethanol (E) group: received a 2 g dose of ethanol/kg in 25% (v/v); and control (C) group: received the same volume of filtered water; both were treated by gavage for 54 days. On the 55th day of the experiment, epididymis, and testis were collected for sperm count, histopathology, mast cell count, and morphometry. The vas deferens was collected for sperm motility analysis. The femur and testicle were used for cytogenetic analysis. Ethanol exposure caused reduction in daily sperm production (DSP) and in sperm motility, multinucleated cells or those having no chromosomal content, and late chromosome migrations. No changes were observed in the number of chromosomes in the mitotic analysis. However, some alterations could be seen in meiocytes at different stages of cell division. Stereological analysis of the epididymis indicated reorganization of its component in the 2A and 5A/B regions. The epididymal cauda had greater recruitment, and both degranulated and full mast cells showed an increase in the initial segment, in the ethanol group. In conclusion, ethanol administration during the pubertal phase affects epididymis and testis in adult rats, as indicated mainly by our new findings related to mast cell number and meiotic impact. Microsc. Res. Tech. 79:541-549, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Etanol/toxicidade , Genitália Masculina/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Animais , Masculino , Mastócitos/citologia , Meiose/efeitos dos fármacos , Mitose/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/citologiaRESUMO
Mast cell proteases are thought to be involved with tumor progression and neo-vascularization. However, their exact role is still unclear. The present study was undertaken to further elucidate the function of specific subtypes of recombinant mouse mast cell proteases (rmMCP-6 and 7) in neo-vascularization. SVEC4-10 cells were cultured on Geltrex® with either rmMCP-6 or 7 and tube formation was analyzed by fluorescence microscopy and scanning electron microscopy. Additionally, the capacity of these proteases to induce the release of angiogenic factors and pro and anti-angiogenic proteins was analyzed. Both rmMCP-6 and 7 were able to stimulate tube formation. Scanning electron microscopy showed that incubation with the proteases induced SVEC4-10 cells to invade the gel matrix. However, the expression and activity of metalloproteases were not altered by incubation with the mast cell proteases. Furthermore, rmMCP-6 and rmMCP-7 were able to induce the differential release of angiogenic factors from the SVEC4-10 cells. rmMCP-7 was more efficient in stimulating tube formation and release of angiogenic factors than rmMCP-6. These results suggest that the subtypes of proteases released by mast cells may influence endothelial cells during in vivo neo-vascularization.
Assuntos
Proteínas Angiogênicas/metabolismo , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Neovascularização Patológica/metabolismo , Triptases/farmacologia , Indutores da Angiogênese/farmacologia , Animais , Linhagem Celular , Células Cultivadas , Embrião de Galinha , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Masculino , Mastócitos/citologia , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , CamundongosRESUMO
Acute inflammatory response after photodynamic therapy is frequently described, and increase on mast cell degranulation is also present during this process. The mast cell activation may improve angiogenesis, and this fact has been associated with progression of oral premalignant lesions (OPL). The aim of this study was to evaluate whether photodynamic therapy (PDT) increases mast cell density (MCD) and microvessels density (MVD) in 4-nitroquinoline-1-oxide(4NQO)-induced OPL in rats. 4NQO-induced OPL were treated or not with 5-ALA followed by laser irradiation (PDT group and 4NQO groups, respectively). Mast cells and CD34+ microvessels were counted. Both PDT and 4NQO groups had MCD and MVD that were higher than normal mucosa (p b 0.05). The 4NQO group had the lowest number of non-degranulated MCD in comparison to experimental periods of PDT (PDT 6 h p=0.020; 24 h p=0.016; 48 h p=0.003; 72 h p=0.033). Only in the PDT group did MCD and MVD have a significant correlation (r= 0.6219, p = 0.010). 5-ALA-mediated PDT modified the MCD and MVD in the induced OPL, leading to degranulation of mast cells and angiogenesis. A PDT protocol with an efficient eradication of the OPL must be adopted considering the angiogenesis potential associated with the mast cell activation after the therapy.
Assuntos
Ácido Aminolevulínico/uso terapêutico , Mastócitos/fisiologia , Microvasos/patologia , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias da Língua/tratamento farmacológico , 4-Nitroquinolina-1-Óxido/toxicidade , Ácido Aminolevulínico/farmacologia , Animais , Antígenos CD34/metabolismo , Degranulação Celular/efeitos dos fármacos , Degranulação Celular/efeitos da radiação , Feminino , Hiperplasia/induzido quimicamente , Hiperplasia/patologia , Lasers , Mastócitos/citologia , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/patologia , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/efeitos da radiação , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Ratos , Ratos Wistar , Língua/patologia , Neoplasias da Língua/induzido quimicamente , Neoplasias da Língua/veterináriaRESUMO
Intrathymic lipid-laden multilocular cells (LLMC) are known to express pro-inflammatory factors that might regulate functional activity of the thymus. However, the phenotype of age-associated intrathymic LLMC is still controversial. In this study, we evaluated LLMC density in the aging thymus and better characterized their distribution, ultrastructure and phenotype. Our results show an increased density of LLMC in the thymus from 03 to 24 months of age. Morphologically, intrathymic LLMC exhibit fibroblastoid fusiform, globular or stellate shapes and can be found in the subcapsular region as well as deeper in the parenchyma, including the perivascular area. Some parenchymal LLMC were like telocytes accumulating lipids. We identified lipid droplets with different electrondensities, lipofuscin granules and autolipophagosome-like structures, indicating heterogeneous lipid content in these cells. Autophagosome formation in intrathymic LLMC was confirmed by positive staining for beclin-1 and perilipin (PLIN), marker for lipid droplet-associated proteins. We also found LLMC in close apposition to thymic stromal cells, endothelial cells, mast cells and lymphocytes. Phenotypically, we identified intrathymic LLMC as preadipocytes (PLIN+PPARγ2+), brown adipocytes (PLIN+UCP1+), macrophages (PLIN+Iba-1+) or pericytes (PLIN+NG2+) but not epithelial cells (PLIN- panCK+). These data indicate that intrathymic LLMC are already present in the young thymus and their density significantly increases with age. We also suggest that LLMC, which are morphologically distinct, establish direct contact with lymphocytes and interact with stromal cells. Finally, we evidence that intrathymic LLMC correspond to not only one but to distinct cell types accumulating lipids.
Assuntos
Metabolismo dos Lipídeos , Fenótipo , Timo/citologia , Timo/metabolismo , Fatores Etários , Animais , Autofagia , Comunicação Celular , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Feminino , Linfócitos/citologia , Linfócitos/metabolismo , Mastócitos/citologia , Mastócitos/metabolismo , Camundongos , Fagossomos/metabolismo , Células Estromais/citologia , Células Estromais/metabolismo , Timócitos/citologia , Timócitos/metabolismoRESUMO
In this study, we examined the treatment and mechanism of BMMSC on a deep II degree scald of the hamster skin. A deep II degree scald model on the skin of 40 hamsters was duplicated and divided randomly into a stem cell plantation group (group A) and model control group (group B). Skin cells were cultured in vitro until the allogeneic BMMSCs of the 5th generation formed with a cell count of 1 x 10(7)/mL. Local injection plus liquid supernatant smearing was used to plant the cells into the position of the scald in the stem cell plantation group. The control group was given an equivalent amount of normal saline to observe the healing action, and 5 samples were taken in each group after 1, 3, 7, and 14 days for hematoxylin and eosin staining for physiological observation. Polymerase chain reaction was used to detect the amount of chymotrypsin in mast cells. The speed of healing in the stem cell transplantation group was greater than that in the control group; staining results showed that the quality of healing in the transplantation group was better than that in the control group. Chymotrypsin expression was detected in both groups, reaching a peak on day 3. BMMSCs can accelerate wound healing, and chymotrypsin in mast cells may participate in the wound healing process.
Assuntos
Células-Tronco Mesenquimais/citologia , Pele/citologia , Lesões dos Tecidos Moles/terapia , Transplante de Células-Tronco , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Quimotripsina/biossíntese , Cricetinae , Diabetes Mellitus Experimental , Modelos Animais de Doenças , Mastócitos/citologia , Mastócitos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Pele/crescimento & desenvolvimento , Lesões dos Tecidos Moles/metabolismo , Lesões dos Tecidos Moles/patologia , Cicatrização/genéticaRESUMO
Mast cells (MCs) are versatile effector and regulatory cells in various physiologic, immunologic, and pathologic processes. In addition to the well-characterized IgE/FcεRI-mediated degranulation, a variety of biological substances can induce MCs activation and release of their granule content. Sex steroids, mainly estradiol and progesterone, have been demonstrated to elicit MCs activation. Most published studies have been conducted on MCs lines or freshly isolated peritoneal and bone marrow-derived MC without addressing gender impact on MC response. Our goal was to investigate if the effect of estradiol, progesterone, testosterone, and dihydrotestosterone (DHT) on MCs may differ depending on whether female or male rats are used as MCs donors. Our results demonstrated that effect of sex steroids on MCs histamine release is dose- and gender-dependent and can be direct, synergistic, or inhibitory depending on whether hormones are used alone or to pretreat MCs followed by substance P-stimulation or upon IgE-mediated stimulation. In contrast, sex steroids did not have effect on the MC expression of the IgE high affinity receptor, FcεRI, no matter female or male rats were used. In conclusion, MCs degranulation is modulated by sex hormones in a gender-selective fashion, with MC from females being more susceptible than MC from males to the effects of sex steroids.